Rat C6 glioma cells contain a beta-adrenergic receptor, stimulation of which leads to an induction of a specific form of cyclic nucleotide phospodiesterase (PDE) and an increase of nerve growth factor content. The induction of PDE is shown to require a rise in cyclic AMP, activation of cAMP-dependent protein kinase, translocation of the catalytic subunit of the kinase to the nucleus, phosphorylation of non-histone chromosomal proteins, and RNA polymerase II. Inhibition of one of these steps by drugs such as colchicine, cordycepin or alpha-amanitin prevents PDE induction. Direct measurement of mRNA levels can be made using cDNA probes. Use of a cDNA probe coding for human pheochromocytoma proenkephalin (PE) has shown that rat brain makes a very similar protein. Chronic treatment of rats with haloperidol for 2-3 weeks leads to a specific increase in striatal PE mRNA with no change occurring in other brain regions. Treatment of bovine adrenal chromaffin cells with 8-Br-cyclic AMP results in an increase of PE mRNA in these cells, which is time- and dose-dependent and not replicated by 8-Br-cyclic GMP. There is a comparable change in the content of enkephalin-like peptides.